The following invention relates to disinfectant compounds that act as biocides to an array of microorganisms. The biocides are comprised of cyclic N-halamines that are biocidal when they come in contact with hallogen-sensitive organisms for a specific contact time. This is achieved by coating the N-halamine on a substrate; such as, but not limited to: glass, metal, wood, plastic, concrete, and fabric.
Current surface contact biocides for the use of producing a sterile environment such as for medical tables, surgical equipment, fabric materials, gloves, catheter tubing, piping, industrial and commercial surfaces, swimming pools, floors, can and bottle liners, food production equipment and liners, and various medical and dental applications do not exist or are severely limited in their biocidal abilities. Most commonly used water-soluble disinfectants which contain free halogen have severely limited lifetimes, produce adverse reactions to their environment, and produce toxic by-products. Disinfectants which do not contain free halogen, such as quaternary ammonium and phenolic compounds, are only effective towards specific organisms, are water soluble, and can cause skin and eye irritation. Commercially employed hydantoins, cyanurates, oxazolidinones (Kaminski et al., U.S. Pat. Nos. 4,000,293 and 3,931,213), imidazolidinones (Worley et al., U.S. Pat. Nos. 4,681,948; 4,767,542; 5,057,612; 5,126,057), and polymeric N-halamines (Worley et al., U.S. Pat. Nos. 5,490,983 and 5,670,646) are much more stable than free halogen, ozone, and chlorine dioxide, and are more versatile than phenolic and quaternary ammonium compounds.
Currently only a few disinfectant surfaces have been prepared, most of which focus on quaternary ammonium compounds (quats) anchored on polymer backbones (Hazziza-Laskar et al., J. Appl. Polym. Sci., 50:651 (1993); Nurdin et al., J. Appl. Polym. Sci., 50:663 (1993); Nurdin et al., J. Appl. Polym. Sci., 50:671 (1993); Hazziza-Laskar et al., J. Appl. Polym. Sci., 58:77 (1995)) which are then cast as films. Although these films are biocidal, their limitations are that they need long contact times to kill the organisms, the surface cannot be reactivated once the biocidal activity is lost, the films are relatively expensive to make, and the films are partially water soluble. Other types of surface active disinfectants are polymeric phosphonium materials (Kanazawa et al., J. Polym. Sci., Part A: Polym. Chem., 31:1467 (1993); J. Appl. Polym. Sci., 52:641 (1994)), modified polyesters, polyethers and benzimidiazoles (Oh et al., J. Appl. Polym. Sci., 52:583 (1994); J. Appl. Polym. Sci., 54:859 (1994); Cho et al., J. Macromol. Sci., Pure Appl. Chem., A32:479 (1995)) which are resistant to several types of microorganisms, but the biocidal moiety cannot be regenerated once exhausted, the films are costly to make, and they can be water soluble.
Therefore, there is a need for a surface active biocide that is inexpensive to manufacture, can regenerate its biocidal activity, is water insoluble when necessary, can kill a broad spectrum of microorganisms, does not affect its environment unfavorably, and requires relatively short contact times to inactivate microorganisms when necessary. There is also a need for the contact biocide to be applied to numerous substrates such as glass, wood, metal, fibrous materials, and concrete to maximize the applications for its use.
The present invention relates to a monomer and its corresponding polymers and copolymers comprising a cyclic N-halamine unit, wherein the cyclic N-halamine unit comprises: a 5-membered ring wherein 3 members of the ring are carbon, 1 member of the ring is a nitrogen heteroatom, and 1 member of the ring is oxygen heteroatom; wherein one carbon member comprises a carbonyl group; wherein one non-carbonyl carbon member is attached to an acryloxymethyl linkage which is substituted with moieties R2, R3, and R4, which moieties are selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; wherein said non-carbonyl carbon member is also joined to a moiety R1 selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine, bromine or hydrogen. The general structure for one embodiment of the monomer is shown below. 
wherein X is chlorine, bromine or hydrogen; R1 is selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; R2, R3 and R4 are each independently selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl. A method of using the monomer of structure I for producing a biocidal material or coating through halogenation with chlorine or bromine is also disclosed. The biocidal material can be applied as a coating or film onto a plurality of substrates useful for their disinfectant properties. The biocidal properties can be regenerated by renewed halogenation in chlorine or bromine solutions.
The present invention also relates to biocidal polymers comprising a cyclic N-halamine unit linked at a carbon atom to a second N-halamine unit via acryloxymethyl linkage wherein each N-halamine unit comprises a 5 membered ring, wherein 3 members of the ring are carbon, 1 member of the ring is nitrogen heteroatom, and 1 member of the ring is oxygen heteroatom; wherein 1 carbon member comprises a carbonyl group; wherein 1 non-carbonyl carbon member is linked to the second N-halamine unit via acryloxymethyl linkage, which linkage is substituted with moieties R2, R3 and R4 each of which are independently selected from the group consisting of hydrogen, C1-C4 alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl; wherein said non-carbonyl carbon member is also joined to an R1 substituent selected from the group consisting of hydroxyl, C1-C4 alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine and bromine.
The invention also relates to biocidal copolymers comprising a cyclic N-halamine monomeric unit linked at a carbon atom by an acryloxymethyl linkage to a second monomeric unit, wherein the second monomeric unit is any polymerizable olefin, e.g., acrylic acid, vinyl acetate, vinyl chloride, styrene, acrylonitrile, propylene, or ethylene; wherein the N-halamine monomeric unit comprises a 5 membered ring, wherein 3 members of the ring are carbon, 1 member of the ring is nitrogen heteroatom, and 1 member of the ring is oxygen heteroatom; wherein 1 carbon member comprises a carbonyl group; wherein I non-carbonyl carbon member is linked to the second monomeric unit via acryloxymethyl linkage, which linkage is substituted with moieties R2, R3 and R4 each of which are independently selected from the group consisting of hydrogen, C1-C4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl; wherein said non-carbonyl carbon member is also joined to an R1 substituent selected from the group consisting of hydroxyl, C1-C4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine and bromine.
The invention also relates to biocidal grafted copolymers comprising a cyclic N-halamine unit linked at a carbon atom by an acryloxymethyl linkage to a polymer backbone wherein the polymer backbone is any commercial polymer, e.g., poly-vinyl chloride, poly-acrylonitrile, poly-vinyl acetate, poly-vinyl alcohol, poly-styrene, cellulose, and cellulose blends with polyester, rayon, spandex, and poly-urethanes; wherein the N-halamine unit comprises a 5 membered ring, wherein 3 members of the ring are carbon, 1 member of the ring is nitrogen heteroatom, and 1 member of the ring is oxygen heteroatom; wherein 1 carbon member comprises a carbonyl group; wherein 1 non-carbonyl carbon member is linked to the polymer via acryloxymethyl linkage, which linkage is substituted with moieties R2, R3 and R4 each of which are independently selected from the group consisting of hydrogen, C1-C4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl; wherein said non-carbonyl carbon member is also joined to a substituent R1 selected from the group consisting of hydroxyl, C1-C4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine and bromine.
The present invention further relates to another monomer and its corresponding polymers and copolymers, the monomer comprising a cyclic N-halamine unit, wherein the cyclic N-halamine unit comprises: a 5-membered ring wherein 3 members of the ring are carbon, 2 members of the ring are nitrogen heteroatoms; wherein two carbon members each comprise a carbonyl group; wherein one nitrogen heteroatom is attached to an acryloxymethyl linkage which is substituted with moieties R3, R4, and R5, which moieties are selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; wherein the remaining non-carbonyl carbon member is also joined to moieties R1 and R2 selected from the group consisting of hydrogen, hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; and wherein the remaining nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine, bromine or hydrogen. The general structure for one embodiment of the monomer is shown as structure IV below. 
A method of using the monomer of structure IV for producing a biocidal material or coating through halogenation with chlorine or bromine is also disclosed. The biocidal material can be applied as a coating or film onto a plurality of substrates useful for their disinfectant properties. The biocidal properties can be regenerated by renewed halogenation in chlorine or bromine solutions.
The present invention further relates to a chemical unit useful to produce monomers and corresponding polymers and copolymers which are used to produce biocides, the unit comprising a cyclic N-halamine unit, wherein the cyclic N-halamine unit comprises: a 5-membered ring wherein 3 members of the ring are carbon, and 2 members of the ring are nitrogen heteroatoms; wherein two carbon members each comprise a carbonyl group; one nitrogen heteroatom is attached to a hydroxymethyl group and the remaining is attached to a hydrogen and the remaining non-carbonyl carbon member is joined to moieties R1 and R2 selected from the group consisting of hydrogen, hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl. The general structure for one embodiment of the unit is shown as structure III below. 
A method of using the unit of structure III for producing monomers by condensation of the unit with a diisocyanate or polyurethane in the presence of a tertiary amine, wherein the monomers are useful in producing biocidal materials and coatings by polymerization, and followed by halogenation with chlorine or bromine, is also disclosed. The biocidal material can be applied as a coating or film onto a plurality of substrates useful for their disinfectant properties. The biocidal properties can be regenerated by renewed halogenation with chlorine or bromine solutions.
The present invention further relates to another monomer and its corresponding polymers and copolymers, the monomer comprising a cyclic N-halamine unit, wherein the cyclic N-halamine unit comprises: a 5-membered ring wherein 3 members of the ring are carbon, and 1 member of the ring is nitrogen heteroatom, and the remaining member of the ring is oxygen heteroatom; wherein one carbon member comprises a carbonyl group; the nitrogen heteroatom is attached to a hydrogen and one of the remaining carbons is attached to 2 hydroxymethyl groups. The general structure for one embodiment of the monomer is shown as structure V below. 
A method of using the monomer of structure V for producing a biocidal material or coating by polymerization with a diisocyanate or polyurethane in the presence of a tertiary amine, followed by halogenation with chlorine or bromine is also disclosed. In one actual embodiment, a diol can be included in the polymerization step. The biocidal material can be applied as a coating or film onto a plurality of substrates useful for their disinfectant properties. The biocidal properties can be regenerated by renewed halogenation in chlorine or bromine solutions.
The invention further relates to a method for disinfecting a habitat for halogen-sensitive microorganisms comprising contacting the habitat with a N-halamine monomer, polymer, copolymer or grafted copolymer as described above.
The present invention provides an improved compound and method of using the same for disinfecting a habitat for halogen-sensitive microorganisms, and further provides novel N-halamine biocidal compounds in surface coatings for disinfection of halogen-sensitive organisms.
The present invention may be understood more readily by reference to the following detailed description of specific embodiments and the Examples and Figures included therein.
As used herein, xe2x80x9cprecursorxe2x80x9d or xe2x80x9cintermediatexe2x80x9d compound can mean a single chemical unit, or its derivatives, a monomer, or its derivatives, or any chain of units, derivatives, and monomers which have been polymerized, co-polymerized, or grafted with each other or with units, derivatives, or monomers.
As used herein, xe2x80x9ccyclic N-halamine unitxe2x80x9d refers to a heterocyclic, monocyclic compound wherein the ring members comprise at least carbon, nitrogen, and oxygen provided there is at least one nitrogen heteroatom; wherein at least one halogen, preferably chlorine or bromine, is bonded to a nitrogen heteroatom; and wherein at least one carbon ring member can comprise a carbonyl group. The presence of the halogen renders it biocidal. The term xe2x80x9ccyclic amine unitxe2x80x9d refers to a heterocyclic, monocyclic compound wherein the ring members comprise at least carbon, nitrogen, and oxygen provided there is at least one nitrogen heteroatom; wherein hydrogen is bonded to a nitrogen heteroatom; and wherein at least one carbon ring member can comprise a carbonyl group. Methods described herein for preparing polymers using cyclic N-halamine monomers can readily be performed with cyclic amine monomers.
Herein, xe2x80x9cpolymerxe2x80x9d and xe2x80x9ccopolymerxe2x80x9d are at times used interchangeably. The use of one or the other term is not meant to be limiting except where indicated by the context.
As used herein, the term xe2x80x9ca polymer comprising a cyclic amine or N-halamine unit joined by a linkage to a second cyclic amine or N-halamine unitxe2x80x9d is not meant to be limiting as to the number of cyclic amine or N-halamine units in a polymer. A xe2x80x9cpolymerxe2x80x9d can comprise two or more cyclic amine or N-halamine units, and the number of units in any given polymer can vary according to the use intended for the polymer. For example, the polymer can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 500, 1000, and so forth, units.
Additionally, a xe2x80x9cpolymer comprising a cyclic amine unit joined by a linkage to a second cyclic amine unitxe2x80x9d or a xe2x80x9cbiocidal polymer comprising a cyclic N-halamine unit joined by a linkage to a second cyclic N-halamine unitxe2x80x9d can further comprise additional, other monomer types, which can be designated monomer xe2x80x9cMxe2x80x9d or monomer xe2x80x9cO,xe2x80x9d for example, for convenience (i.e., a copolymer). Each cyclic amine or N-halamine unit in the polymer can be identical or they can vary. A polymer/copolymer can comprise, for example, one, two, three, four, five, ten or more different monomers. The monomers can be arranged in random arrangement or in block arrangement. A xe2x80x9cbiocidal polymerxe2x80x9d of this invention can comprise one or more biocidal cyclic N-halamine units, i.e., halogenated cyclic amine units.
As used herein, a xe2x80x9cbiocidal N-halamine copolymer comprising N-halamine unit joined by an acryloxymethyl linkage to a second monomeric unitxe2x80x9d is not meant to be limiting as to the number of cyclic N-halamine units in a polymer, nor is it meant to suggest that each cyclic N-halamine unit is linked to a different monomeric unit. It refers to a copolymerization of the cyclic amine with one or more different monomeric units in a controlled or random array in the polymer. A xe2x80x9ccopolymerxe2x80x9d can comprise two or more cyclic N-halamine units, and one or more different monomeric units and the number of units in any given copolymer can vary according to the use of the copolymer.
The copolymer can be prepared in bulk, solution, emulsion, or suspension depending on the application desired. A xe2x80x9cbulkxe2x80x9d copolymerization can comprise cyclic amine monomer and at least one other monomer wherein the polymerization occurs in the absence of solvent. A xe2x80x9csolutionxe2x80x9d copolymerization can comprise cyclic amine monomer and at least one other monomer wherein the polymerization occurs in a solvent, either organic or inorganic. An xe2x80x9cemulsionxe2x80x9d copolymerization can comprise cyclic amine monomer and at least one other monomer wherein the polymerization occurs where water is the solvent along with a surfactant. A xe2x80x9csuspensionxe2x80x9d copolymerization can comprise cyclic amine monomer and at least one other monomer wherein the polymerization occurs where water is the solvent. Each cyclic N-halamine unit and monomeric unit in the copolymer can be identical. A xe2x80x9clatexxe2x80x9d is any polymer that is emulsified in water via surfactant or any other emulsifying agent. An example of the nomenclature used throughout for all copolymerizations goes as follows: poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone.
As used herein, a xe2x80x9cbiocidal N-halamine grafted copolymer comprising a N-halamine unit joined by an acryloxymethyl linkage to a polymer backbonexe2x80x9d is not meant to be limiting as to the number of cyclic N-halamine units in a polymer, nor is it meant to suggest that each cyclic N-halamine unit is directly linked to the polymer backbone. It refers to chemically grafting two or more cyclic amine units on to a pre-existing polymeric backbone in a specific or random arrangement. A xe2x80x9cgrafted copolymerxe2x80x9d can comprise a polymer backbone wherein the polymer is comprised of one or more monomeric units which can be polymeric cyclic N-halamines. A grafting reaction can occur in solution or bulk. Each cyclic N-halamine unit and polymeric backbone in the grafted copolymer can be identical, they can be repeat motifs of two or more units, or they can be a random arrangement of two or more different units. An example of the nomenclature used throughout for all grafting reactions is as follows: poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone.
As used herein, a xe2x80x9chabitat for halogen-sensitive microorganismsxe2x80x9d is any substance in which or on which such organisms are capable of survival for a predetermined and undesirable period of time.
Cyclic organic N-halamine compounds having two alkyl substituent groups substituted on the ring carbons adjacent to the Nxe2x80x94Cl and Nxe2x80x94Br moieties exhibit long-term stability in aqueous solution and release little or no free halogen, while providing adequate disinfection efficacy. Additionally, because polymeric molecules can be constructed to have low solubility in water, an insoluble cyclic N-halamine polymer containing similar cyclic N-halamine structural groups is an ideal polymeric biocide.
A strategy for incorporating cyclic N-halamine structural groups into polymers is: an existing cyclic amine or amide such as those described by Worley in U.S. Pat. Nos. 4,681,948; 4,767,542; 5,057,612; 5,126,057 is functionalized with a polymerizable moiety such as a vinyl group and then polymerized and halogenated. The insoluble cyclic N-halamine polymers inactivate microorganisms once applied to a substrate upon contact, release minimal amounts of free halogen and other leachable impurities, and can be prepared or regenerated by applying diluted solutions of free halogen to the coated substrate containing the cyclic amine or amide.
A second strategy for incorporating cyclic N-halamine structural groups into polymers is to modify an existing polymer by linking a biocidal moiety to it as in Worley U.S. Pat. No. 5,490,983. The former strategy is more preferable in the current embodiment.
The novel N-halamine biocidal polymers described herein contain heterocyclic units which have stable Nxe2x80x94Cl or Nxe2x80x94Br chemical bonds necessary for biocidal action. The heterocyclic N-halamine units can comprise 5 membered rings, wherein at least one heteroatom is nitrogen and at least one heteroatom is oxygen, and which can have one carbonyl group. A carbon atom of these heterocyclic moieties can be joined by a linkage to an additional heterocyclic N-halamine unit by one of many possible linkages which attach to each N-halamine unit at a single non-carbonyl carbon atom, such as by a lower alkyl, i.e., a three to eleven carbon chain that can be branched when greater than three carbons, or a phenyl-lower alkyl-phenyl i.e., two phenyl groups joined by a three to eleven carbon chain that can be branched when greater than three carbons wherein one phenyl attaches to a cyclic N-halamine unit and the other phenyl attaches to a neighboring cyclic N-halamine unit.
Specifically, compounds can include biocidal monomers comprising a cyclic N-halamine unit wherein the cyclic N-halamine unit comprises: a 5-membered ring, wherein at least 3 members of the ring are carbon, 1 member of the ring is nitrogen heteroatom, and 1 member is oxygen heteroatom; wherein 1 carbon member comprises a carbonyl group; wherein one non-carbonyl carbon member is attached to an acryloxymethyl linkage which is substituted with moieties R2, R3, and R4, which moieties are selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; wherein said non-carbonyl carbon member is also joined to a moiety R1 selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine and bromine.
Thus the present invention provides a monomer and its corresponding polymers and copolymers comprising a cyclic N-halamine unit, wherein the cyclic N-halamine unit comprises: a 5-membered ring wherein 3 members of the ring are carbon, 1 member of the ring is a nitrogen heteroatom, and 1 member of the ring is oxygen heteroatom; wherein 1 carbon member comprises a carbonyl group; wherein one non-carbonyl carbon member is attached to an acryloxymethyl linkage which is substituted with moieties R2, R3, and R4, which moieties are selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; wherein said non-carbonyl linkage carbon member is also joined to a moiety R1 selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine, bromine or hydrogen. A general structure for one embodiment of the monomer is shown below. 
wherein X is chlorine, bromine or hydrogen; R1 is selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; R2, R3 and R4 are each independently selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl. The monomer is biocidal when X is chlorine or bromine.
Compounds also include biocidal polymers comprising a cyclic N-halamine unit linked at a carbon atom by acryloxymethyl linkage to a second cyclic N-halamine unit, wherein each cyclic N-halamine unit is a 5-membered ring, wherein 3 members of the ring are carbon, and 1 member of the ring is nitrogen heteroatom; wherein 1 member of the ring is oxygen heteroatom; wherein 1 carbon member comprises a carbonyl group; wherein 1 non-carbonyl carbon member is attached to an acryloxymethyl linkage which is substituted with moieties R2, R3, and R4, which moieties are selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; wherein said non-carbonyl linkage carbon member is also joined to a moiety R1 selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl; and wherein the nitrogen heteroatom is joined to a moiety X selected from the group consisting of chlorine, bromine or hydrogen.
Compounds also include biocidal copolymers comprising one or more cyclic N-halamine units linked at a carbon atom by acryloxymethyl linkage to a second monomeric unit, wherein the second monomeric unit can be any polymerizable olefin.
Compounds also include biocidal grafted copolymers comprising one or more cyclic N-halamine units linked at a carbon atom by acryloxymethyl linkage to a pre-existing polymer backbone, wherein the polymeric backbone can be any commercial polymer.
Examples of the aforementioned polymers, copolymers and grafted copolymers include, but are not limited to, polymers, copolymers and grafted copolymers comprising one or more cyclic amine and N-halamine monomers represented by the repeating unit graphic formula illustrated below. 
wherein X is selected from the group consisting of hydrogen, chlorine, and bromine but when X is hydrogen, no biocidal activity is imparted; wherein R1 is selected from the group consisting of hydroxyl, C1-C4 alkyl, benzyl, substituted benzyl, phenyl, substituted phenyl, and any combination thereof; and wherein R2, R3, and R4 are each independently selected from the group consisting of hydrogen, C1-C4 alkyl, benzyl, substituted benzyl, phenyl, and substituted phenyl.
The alkyl substituents representing R1, R2, R3, and R4 or those attached to phenyl or benzyl may contain from 1 to 4 carbon atoms, including methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, secondary butyl, and tertiary butyl. As shown by the graphic formulae, the linkages between two cyclic N-halamine units can be a xe2x80x9clower alkylxe2x80x9d defined as a hydrocarbon chain, branched or unbranched, having three carbon atoms. For example, a structure II polymer may contain a three carbon linkage, wherein R1 is methyl, and R2, R3, and R4 are hydrogen.
Examples of the aforementioned compounds for each structure type include, but are not limited to: structure I: 3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; 3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; structure II: poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-3-bromo-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone; poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-acrylonitrile-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-acrylic acid-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-styrene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-vinyl acetate-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-vinyl chloride-co-3-chloro-4-(acryloxy-methyl)-4-ethyl-2-oxazolidinone; poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-vinyl chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-vinyl acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone; poly-vinyl alcohol-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone.
By substitution of other named substituents for R1, R2, R3, and R4, e.g., propyl, phenyl, etc., for one or more of the derivatives above named, other correspondingly named N-halo derivatives may be formed.
The polymeric N-halamine biocidal compounds of the present invention can be prepared by reacting the corresponding unhalogenated polymers, herein referred to as xe2x80x9cprecursor cyclic aminesxe2x80x9d or xe2x80x9ccyclic amines,xe2x80x9d with a source of chlorine or bromine. While chlorine gas or liquid bromine may be utilized, other milder halogenating agents such as, but not limited to, calcium hypochlorite, sodium hypochlorite, N-chlorosuccinimide, N-bromosuccinimide, sodium dichloroisocyanurate, trichloroisocyanuric acid, tertiary butyl hypochlorite, N-chloroacetamide, N-chloramines, N-bromamines, etc., can also be employed. Halogenation of the unhalogenated compounds can be accomplished in aqueous media, in mixtures of water with common inert organic solvents such as methylene chloride, chloroform, and carbon tetrachloride, in inert organic solvents themselves, or with no solvent present, at room temperature. The precursor cyclic amines can be a previously utilized cyclic N-halamine that has become ineffective at killing microorganisms due to inactivation of the Nxe2x80x94Cl or Nxe2x80x94Br moieties. The above-described halogenations can be performed in situ, if desired.
The unhalogenated precursor cyclic amines described in this invention can be prepared from existing inexpensive commercial grade starting materials. In the case of the structure represented above by structure I, commercial grade 2-amino-2-alkyl-1,3-propanediols can be reacted with dialkyl carbonates in the presence of sodium methoxide or sodium ethoxide as a catalyst in common solvents in a cyclization reaction to produce the 4-alkyl-4-hydroxymethyl-2-oxazolidinone, followed by reaction with acryloyl chloride, or substituted acryloyl chlorides in common solvents such as chloroform, methylene chloride, benzene, toluene, acetone, etc., to produce the 4-(acryloxymethyl)-4-alkyl-2-oxazolidinone. Those who are skilled in the art know that the 4-alkyl-4-hydroxymethyl-2-oxazolidinone could be prepared by other synthetic strategies. For the structures represented by structure II, the compounds encompassing those in structure I are homopolymerized in the presence of an organic soluble initiator, such as, but not limited to, 1,1xe2x80x2-azobis(cyclohexanecarbonitrile), 2,2xe2x80x2-azobisisobutyronitrile, substituted 2,2xe2x80x2-azobisisobutyronitrile, benzoyl peroxide, substituted benzoyl peroxide, etc., or a water soluble initiator, such as, but not limited to, hydrogen peroxide, ammonium persulfate, sodium persulfate, potassium persulfate, etc., in the presence of a surfactant, such as, but not limited to, sodium laurel sulfate, ammonium laurel sulfate, etc., when water is used as the solvent, and in common solvents such as, chloroform, methylene chloride, carbon tetrachloride, dimethylformamide, etc. For copolymerizations, the compounds encompassing those in structure I-type are copolymerized with various monomers, such as, but not limited to, acrylonitrile, acrylic acid, ethylene, propylene, styrene, vinyl acetate, vinyl chloride, etc., in the presence of an initiator as mentioned above, in solvents as mentioned above, and with a surfactant as mentioned above. For grafting reactions, the compounds encompassing structure I-type are grafted on to polymeric backbones, such as, but not limited to, poly-acrylonitrile, poly-acrylic acid, poly-styrene, poly-vinyl acetate, poly-vinyl alcohol, poly-vinyl chloride, etc., in the presence of an initiator as mentioned above, with the addition of a surfactant as mentioned above. The polymeric backbone is in latex form, which means it is emulsified in water prior to the grafting reaction either with surfactants for water soluble polymers, i.e., poly-vinyl alcohol, poly-acrylic acid, etc., or for water insoluble polymers, i.e., poly-acrylonitrile, poly-vinyl chloride, poly-styrene, etc.; the corresponding monomers, i.e., acrylonitrile, vinyl chloride, styrene, etc., are polymerized in an emulsion prior to the grafting reaction.
The present invention further provides a method for disinfecting a habitat for halogen-sensitive microorganisms comprising contacting the habitat with a biocidal amount of a biocidal monomer as described herein. For example, the biocidal monomer can be any of the following, used singly or in combination:
3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
3-chloro-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
3-chloro-4-(2xe2x80x2-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
3-chloro-4-(3xe2x80x2,3xe2x80x2-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone,
3-bromo-4-( acryloxymethyl)-4-ethyl-2-oxazolidinone,
3-bromo-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
3-bromo-4-(2xe2x80x2-methylacryloxymethyl)-4-ethyl-2-oxazolidinone, and
3-bromo-4-(3xe2x80x2,3xe2x80x2-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone.
The present invention further provides a method for disinfecting a habitat for halogen-sensitive microorganisms comprising contacting the habitat with a biocidal amount of a biocidal polymer as described herein. For example, the biocidal polymer can be any of the following, used singly or in combination:
poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-chloro-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-chloro-4-(2xe2x80x2-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-chloro-4-(3xe2x80x2,3xe2x80x2-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-styrene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl acetate-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl chloride-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-ethylene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-propylene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl alcohol-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-ethylene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-propylene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
cellulose-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-bromo-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-bromo-4-(2xe2x80x2-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-3-bromo-4-(3xe2x80x2,3xe2x80x2-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-acrylonitrile-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-styrene-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl acetate-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl chloride-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-ethylene-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-propylene-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-acrylonitrile-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-styrene-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl acetate-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl alcohol-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-vinyl chloride-g-3-bromo-4-(acryloxymethyl)4-ethyl-2-oxazolidinone,
poly-ethylene-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
poly-propylene-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone, and
cellulose-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone.
The cyclic N-halamine biocidal compounds can be made soluble or insoluble in water depending on the application desired. They can be employed as disinfectants against undesirable microorganisms in many habitats including surfaces of materials by treating the material with a biocidally effective amount of polymer compound. Water insoluble biocidal surfaces can include the following applications: for example, oil and water based paints, catheters, surgical tables, surgical instrumentation, medical tables and desktops, medical instrumentation, dental tables and desktops, dental instrumentation, swimming pool liners, fabric materials, medical wrappings, piping, workbenches, counter tops, and the like. Water soluble biocidal surfaces can include the following applications, for example, oil and gas tank liners, preservatives, can and bag liners, water based paints, and the like. As used herein, a xe2x80x9csurfacexe2x80x9d can include any surface upon which halogen-sensitive microorganisms can dwell and to which a claimed polymer can be bound, which can include surfaces of, for example, textile fabric, metal, rubber, concrete, wood, glass, bandaging, and plastic.
For surfaces, disinfection testing is best accomplished by placing microbiologically contaminated water onto the polymer coated substrate. The contact time will be measured, which is the amount of time needed for the surface to kill a substantial amount of the microorganism; depending on the application, the contact times will vary. These polymeric biocides can be incorporated into textile and solid surfaces which can serve as disinfectants or biological preservatives.
Once a surface becomes ineffective at killing microorganisms due to inactivation of the Nxe2x80x94Cl or Nxe2x80x94Br moieties, it can be regenerated by wiping an aqueous solution of free halogen over it. Additionally, the cyclic N-halamine biocide can be created or regenerated in situ by adding a stoichiometric amount of free halogen, either chlorine or bromine, to a precursor cyclic amine contained in a material such as in paint, oil, textile fabric or the like, or bound to a surface of a material such as wood, glass, plastic polymer coating, textile fabric, metal, rubber, concrete, cloth bandage, or the like.
All microorganisms on hard surfaces susceptible to disinfection by free halogen, e.g., free chlorine, or combined halogen, e.g., N-haloimidazolidinones, N-halohydantoins, N-halooxazolidinones, N-haloisocyanurates, etc., will also be susceptible to disinfection by the biocidal compounds of this invention. Such microorganisms include, for example, bacteria, protozoa, fungi, viruses, and algae.
The biocidal compounds described herein can be employed in a variety of disinfecting applications. They will be of importance in controlling microbiological contamination on surfaces, for medical and dental applications, bandages, fabric materials, piping, paints, swimming pools, catheters, and the like. For example, the halogenated polymers will prevent the growth of undesirable organisms, such as the bacteria genera Staphylococcus, Pseudomonas, Salmonella, Shigella, Legionella, Methylobacterium, Klebsiella, and Bacillus; the fungi genera Candida, Rhodoturula, and molds such as mildew; the protozoa genera Giardia, Entamoeba, and Cryptosporidium; the viruses poliovirus, rotavirus, HIV, and herpesvirus; and the algae genera Anabaena, Oscillatoria, and Chlorella; and other sources of biofouling on surfaces. They will be of importance as preservatives and preventatives against microbiological contamination in paints, coatings, and on surfaces. They will be of particular importance to the medical field for use in ointments, bandages, sterile surfaces, and the like, and for the attachment to liners of containers used in the food processing industry. They can be used in conjunction with textiles for sterile applications, such as coatings or physical bonds to sheets or bandages used for burn victims or on microbiological decontamination suits.
The halogenated compounds described herein can be used in diverse liquid and solid formulations such as powders, granular materials, solutions, concentrates, emulsions, slurries, and in the presence of diluents, extenders, fillers, conditioners, aqueous solvent, organic solvents, plasticizers, pigments, and the like. Of particular use can be their employment in formulations involving wetting emulsifying, or dispersing agents such as sulfonates, alcohols, or similar surface active materials. The compounds are also compatible with buffering agents and other sources of halogen.
A further embodiment of biocidal compounds made in accordance with the invention uses monomers of:
3-hydroxymethyl-5,5-dimethylhydantoin (Structure III, wherein R1 and R2 are methyl), 
3-(acryloxymethyl)-5,5-dimethylhydantoin (Structure IV, wherein R1 and R2 are methyl, and R3, R4, and R5 are hydrogen) and, 
4,4-dihydroxymethyl-2-oxazolidinone (Structure V) 
in synthesizing polymers, copolymers, and grafted copolymers which can be coated onto surfaces and upon halogenation with free chlorine or bromine, become biocidal. Of particular importance is the use of these monomers in the preparation of the N-chlorinated copolymers of 3-(acryloxymethyl)-5,5-dimethylhydantoin and methyl methacrylate/2-hydroxyethyl acrylate or methyl methacrylate/acrylic acid for biocidal thermosetting coatings, and in the preparation of N-chlorinated copolymers of 4,4-dihydroxymethyl-2-oxazolidinone and diisocyanates. The latter class of compounds is preferably used for biocidal polyurethane coatings.